C3 and C6 Modification-Specific OYE Biotransformations of Synthetic Carvones and Sequential BVMO Chemoenzymatic Synthesis of Chiral Caprolactones.
C3 and C6 Modification-Specific OYE Biotransformations of Synthetic Carvones and Sequential BVMO Chemoenzymatic Synthesis of Chiral Caprolactones.
复制标题
合成香芹酮的 C3 和 C6 修饰特异性 OYE 生物转化和手性己内酯的连续 BVMO 化学酶合成。
DOI：
10.1002/chem.201805219
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Issa IS
中科院分区：
文献类型：
--
作者：
Issa IS
The scope for biocatalytic modification of non‐native carvone derivatives for speciality intermediates has hitherto been limited. Additionally, caprolactones are important feedstocks with diverse applications in the polymer industry and new non‐native terpenone‐derived biocatalytic caprolactone syntheses are thus of potential value for industrial biocatalytic materials applications. Biocatalytic reduction of synthetic analogues ofR‐(−)‐carvone with additional substituents at C3 or C6, or both C3 and C6, using three types of OYEs (OYE2, PETNR and OYE3) shows significant impact of both regio‐substitution and the substrate diastereomer. Bioreduction of (−)‐carvone derivatives substituted with a Me and/or OH group at C6 is highly dependent on the diastereomer of the substrate. Derivatives bearing C6 substituents larger than methyl moieties are not substrates. Computer docking studies of PETNR with both (6S)‐Me and (6R)‐Me substituted (−)‐carvone provides a model consistent with the outcomes of bioconversion. The products of bioreduction were efficiently biotransformed by the Baeyer–Villiger monooxygenase (BVase) CHMO_Phi1 to afford novel trisubstituted lactones with complete regioselectivity to provide a new biocatalytic entry to these chiral caprolactones. This provides both new non‐native polymerization feedstock chemicals, but also with enhanced efficiency and selectivity over native (+)‐dihydrocarvone Baeyer–Villigerase expansion. Optimum enzymatic reactions were scaled up to 60–100 mg, demonstrating the utility for preparative biocatalytic synthesis of both new synthetic scaffold‐modified dihydrocarvones and efficient biocatalytic entry to new chiral caprolactones, which are potential single‐isomer chiral polymer feedstocks.
